tbuckley/cabot-search huggingface dataset:
Abstract 12710: Adipocyte-Derived Exosomal Lncrna Sbf2-as1 Promotes Diabetic Myocardial Fibrosis Through Regulating Hnrnpa1/nrf2 Pathway via Sumoylation
Authors: Yue Guo, Zhuohui Chen, Lingling Wu, Xiaodong Zhuang, Xinxue Liao
Journal: Circulation (2022)

Introduction: The inhibition of Nrf2 pathway is regarded as the dominant process that correlates with the pathogenesis of diabetic cardiomyopathy (DCM). Recently, accumulating evidence reveals that lncRNAs play key roles in regulating Nrf2 pathway. However, the underlying mechanisms remain unclear. Here, we found that adipocyte lncRNA SBF2-AS1 (SBF2-AS1) enhanced the SUMOylation of hnRNPA1, which subsequently facilitated the package of SBF2-AS1 into exosomes under high glucose conditions. Hypothesis: We hypothesized that AdEXO-SBF2-AS1 promotes diabetic myocardial fibrosis through regulating the hnRNPA1/Nrf2 pathway via SUMOylation. Methods: We examined the effect of exosomes from diabetic (db/db) mice-derived adipocytes on ANG-II-induced cardiac fibrosis and function in non-diabetic mice. In the invitro study, HG (33mmol/L)-induced AdEXO were cultured with adult human cardiac fibroblasts (aHCFs). Differentially expressed lncRNAs in AdEXO were screened using lncRNA sequencing. Results: Intramyocardial injection of diabetic AdEXO in the non-diabetic heart exacerbated myocardial fibrosis. Whereas administration of an exosomes biogenesis inhibitor attenuated cardiac fibrosis in diabetic mice. We identified SBF2-AS1 is a common molecule significantly increased in diabetic AdEXO and HG-stimulated non-diabetic AdEXO. After four weeks of ANG II infusion, EXO-db/dbWT-injected mice displayed significant fibrosis in the heart. However, interestingly, mice receiving SBF2-AS1-deficient db/db-EXO showed a decrease in cardiac fibrosis. Similarly, AdEXO-SBF2-AS1 promoted aHCFs proliferation and transformation capabilities in vitro. Mechanistically, SBF2-AS1 induced UBC9 overexpression to catalyze the SUMOylation of hnRNPA1, which facilitated its packaging into exosomes. Subsequently, exosomal SBF2-AS1 was specifically transmitted into aHCFs and epigenetically downregulated Nrf2 expression by decreasing H3K9 acetylation level in the Nrf2 promoter. Conclusions: Our findings highlight a novel mechanism whereby the AdEXO-mediated SBF2-AS1/hnRNPA1/Nrf2 regulatory axis promotes diabetic myocardial fibrosis in a SUMOylation-dependent manner and implicate SBF2-AS1 as an attractive therapeutic target for DCM.
Abstract 14275: Sex Disparity of Cardiovascular Risk in Organisation for Economic Co-Operation and Development Countries (OECD): Finding the “Real Difference” Between Males and Females
Authors: Rohan Bhattaram, Siddharth Bhayani, Mladen I Vidovich
Journal: Circulation (2022)

Background: The differences in cardiovascular risk between males and females has been well established and the real difference (utilizing the natural log function) has been used to describe sex differences in incidents like motor vehicle accident rates. However, the “real difference” has not been applied to cardiovascular outcomes previously. The purpose of this study was to apply the “real difference” to cardiovascular death rates while evaluating the relationship between the “real difference” and established economic markers. Methods: OECD Statistics, a freely available online database, was accessed for data retrieval. Male and female cardiovascular death statistics (per 100,000) in all 38 OECD countries were acquired from the freely available online database, OECD Statistics. The real difference was calculated using Ln(Male CVD Rate) - Ln(Female CVD). A multivariate analysis was run to establish the relationships between different economic markers and the calculated “real difference”. Results: Mexico was found to have the smallest real difference at 0.211 while France had the largest real difference at 0.542. Figure 1 demonstrates the variation between real and raw difference for each country. Multi-variate analysis revealed a significant effect on real difference ( F (32)=4.185, p&lt;0.01) with 40% (R 2 =0.395) of the variation explained by the following factors- Estimated Female Earned Income (US$ PPP), Life Expectancy Gap, % of Women of Total Employment, Wage Gap, and Government Representation of Women. Discussion: The results of the multi-variate analysis demonstrate that sex disparities in cardiovascular death is related to the combined effects of multiple economic factors. The real difference is a valuable metric for assessing sex disparities and further studies should be conducted to further elucidate and account for the difference in CV mortality in different countries.
Abstract 12758: Maternal Gestational Diabetes is Associated With Increased Aortic Stiffness in Pre-Adolescent Children
Authors: Cleighton Boehme, Martha Moran, Victor Do, Juliana Lasso-Mendez, Rhonda C Bell, Deborah S Fruitman, Christy-Lynn Cooke, Lisa K Hornberger
Journal: Circulation (2022)

Introduction: Population studies have suggested adults born to mothers with gestational diabetes mellitus (GDM) have increased risk of cardiovascular (CV) disease. Whether GDM exposure before birth is associated with abnormal CV health in childhood is unknown. In the present study, we prospectively explored the CV health of children of mothers with GDM (CGDM) with comparison to children of healthy mothers (controls) and examined relationships with maternal variables. Methods: CGDM and age- and sex-matched controls were recruited from the longitudinal Alberta Pregnancy Outcomes and Nutrition Birth Cohort Study and underwent CV assessments. Outcome measures included left ventricular mass Z-score, EndoPAT reactive hyperemia index score (endothelial function), Doppler-based aortic and peripheral (common carotid to posterior tibial artery) pulse wave velocity (PWV), and carotid intima-media thickness. CGDM were further stratified into groups according to how maternal GDM was controlled (diet vs insulin). The mother’s pre-pregnancy body mass index (BMI), adherence to the 2007 Canada’s Food Guide, and intake of less healthy foods in the 2 nd and 3 rd trimesters of pregnancy were also examined. Results: We assessed 25 CGDM and 27 controls (mean age 10.9±0.7 years) with comparable birth and baseline characteristics (Table). Aortic PWV was higher in CGDM vs controls (p=0.03), and higher in CGDM of insulin vs diet controlled mothers (p=0.03). No other measures of CV health differed. Mothers with GDM, but not controls, showed evidence of dietary improvement from the 2 nd to 3 rd trimester with improved adherence and reduced less healthy foods. Maternal BMI was unrelated to the child’s CV health. Conclusions: Even with maternal dietary improvement, CGDM have increased aortic stiffness, highest in offspring of mothers managed with insulin. Further work is needed to investigate the mechanisms by which GDM impacts the child’s vascular health and long-term implications.
Abstract 13150: Risk Factors Associated With Major Adverse Cardiovascular Events Following First-Ever Ischemic Stroke: An Observational Study Using Linked Data From an Australian Stroke Registry
Authors: Ajay S Dharan, Lachlan L Dalli, Monique F Kilkenny, Muideen T Olaiya, Dominique A Cadilhac, Lee Nedkoff, Joosup Kim, Nadine E Andrew, Vijaya Sundararajan, Lisa Kuhn
Journal: Circulation (2022)

Introduction: Survivors of stroke are at increased risk of experiencing subsequent major adverse cardiovascular events (MACE). We aimed to determine the incidence of MACE within two years following first-ever ischemic stroke and identify associated factors. Methods: Patient-level data from the Australian Stroke Clinical Registry (2009-2013) were linked with emergency department and hospital admission data. Patient comorbidities were identified in the emergency and admissions data using published algorithms. Adults with no prior history of acute cardiovascular events were followed for two years post-discharge, or until first occurrence of MACE, whichever occurred earlier. Multivariable competing risks regression, accounting for deaths due to non-cardiovascular causes, was used to determine factors associated with MACE post-stroke. Results: Among 5,994 patients with first-ever ischemic stroke (median age 73 years, 45% female), 17% were admitted for MACE (129/100,000 person-years). MACE incidence was greatest in the first year following stroke (157/100,000 person-years). Compared to participants aged ≥65 years, the median time to first MACE was 37 days earlier for those aged &lt;65 years. As there was a significant interaction (p&lt;0.05) between age and other factors in predicting MACE incidence, subsequent analyses were stratified by age group. Being discharged to inpatient rehabilitation (sub-distribution hazard ratio [SHR]: 0.63; 95% Confidence Interval (CI): 0.44-0.90) was associated with reduced risk of MACE in patients aged &lt;65 years only. Whereas, in those aged ≥65 years, MACE was associated with being female (SHR: 1.04; 95% CI: 1.03-1.05), initial stroke severity (SHR: 1.33; 95% CI: 1.15-1.54), smoking (SHR: 1.41; 95% CI: 1.14-1.71), and atrial fibrillation (SHR: 1.31; 95% CI: 1.14-1.51). Being treated in a large hospital (&gt;300 beds) was associated with a lower risk of MACE in those aged &lt;65 (SHR: 0.68; 95% CI: 0.44-0.90) and ≥65 years (SHR: 0.74; 95% CI: 0.62-0.87). Conclusion: MACE presentations are common within two-years of stroke, with most events occurring in the first year. We have identified factors (e.g., use of rehabilitation among younger patients) to consider when designing interventions to prevent MACE after stroke.
Abstract 12936: Higher In-Hospital Mortality After TAVR and PCI on Same Hospitalization: A Systematic Review and Meta-Analysis
Authors: Mateus de Miranda Gauza, Pedro Abi-Kair Borges Calomeni, Nicole Felix, Marina Machado, Pedro Melo
Journal: Circulation (2022)

Introduction: Aortic stenosis (AS) patients admitted for elective transcatheter aortic valve replacement (TAVR) frequently present significant coronary artery disease (CAD). Despite the increasing number of TAVR procedures, it remains unclear if the strategy of performing percutaneous coronary intervention (PCI) and TAVR during the same hospitalization differs from isolated TAVR. Methods: We performed a systematic review and meta-analysis of observational studies in patients with AS and significant CAD (lesions ≥50%). The aim of the study was to compare TAVR and PCI on same hospitalization (with no regard for whether in the same procedure) to TAVR and deferred PCI. In-hospital mortality, acute kidney injury and major bleeding were our outcomes of interest. Results: We included 4 studies with 2917 patients, 665 treated with TAVR+PCI and 2252 treated with TAVR alone. TAVR+PCI was associated with higher in-hospital mortality (OR 1.66; 95% CI 1.21 - 2.27; p=0.002; Fig. 1). However, there was no difference in acute kidney injury (OR 0.59; 95% CI 0.26 - 1.32; p=0.20; Fig. 2A). Furthermore, TAVR+PCI seemed to lower the rate of major bleeding (OR 0.65; 95% CI 0.46 - 0.93; p=0.02 Fig. 2B). Conclusions: In this meta-analysis of retrospective studies, TAVR and PCI on same hospital admission was associated with higher in-hospital mortality when compared to isolated TAVR.
Abstract 14106: Prevalence and Respective Predictive Value of Late Gadolinium Enhancement Phenotypes in Patients Referred for Suspected Infiltrative Cardiomyopathy
Authors: Bradley Sarak, Steven Dyskstra, Jacqueline Flewitt, Alessandro Satriano, Sandra Rivest, Andrew G Howarth, Carmen P Lydell, Robert J Miller, Nowell M Fine, James A White
Journal: Circulation (2022)

Introduction: The respective value of different late gadolinium enhancement (LGE) phenotypes in patients with suspected infiltrative cardiomyopathy remains uncertain. Methods: In a large cohort of patients referred for suspected infiltrative cardiomyopathy, we evaluated respective associations between the dominant LGE phenotype and the composite endpoint of heart failure hospitalization, survived cardiac arrest or death. Kaplan-Meier survival curves were executed for six pre-defined LGE phenotypes. Multivariable analysis was performed to assess their independent association with the composite outcome, adjusted for relevant confounders. Final diagnosis was adjudicated using standardized disease-specific criteria. Results: 588 patients (68% male, median age 70 years, mean LVEF 54.7±12.7%) were studied. Of these patients, 139 (24%) were confirmed to have cardiac amyloidosis (CA) (81 [58%] transthyretin, 54 [39%] light chain and 4 [3%] undifferentiated) by objective non-CMR diagnostic criteria. Any LGE was present in 394 patients (67%) with the dominant phenotype being diffuse in 137 (23%), mid-wall patchy in 118 (20%), ischemic in 55 (9.4%), subepicardial in 18 (3.1%), mid-wall striae in 8 (1.4%), and RV insertion site in 58 (9.9%). The sensitivity and specificity of diffuse LGE for CA was 86% and 96%, respectively. Over a median 855 (IQR 372, 1542) days, 239 (41%) experienced the primary outcome. Unadjusted survival curves for each LGE phenotype are shown in the Figure. Following adjustment, diffuse (HR 2.30, p&lt;0.001), mid-wall patchy (HR 1.52, p=0.040) and ischemic LGE (HR 1.78, p=0.023) remained independently associated (Figure). Conclusions: In patients referred for suspected infiltrative cardiomyopathy, diffuse, mid-wall patchy and ischemic patterns all showed independent prognostic value. We confirm that diffuse LGE pattern reliably identifies CA patients with high sensitivity and specificity while delivering strong prognostic value.
Abstract 13658: Impact of Risk Factors for Atrial Fibrillation on the Incidence of Stroke in African American Females
Authors: Jin Yi, John Gharbin, Ayman Elawad, Ahmed Brgdar, Fariba Yazdanpanah, Mohamed TAHA, Deborah Williams
Journal: Circulation (2022)

Background: It is well-known that African American (AA) patients with Atrial Fibrillation (AF) have a higher incidence of stroke in comparison to the general population. To our knowledge, limited data exist on gender disparities in risk factors contributing to a higher incidence of stroke among AA patients. The objective of this study is to identify gender disparities in risk factors for AF by comparing AA females and males with AF. Methods: AA patients aged 18 years old or above with a diagnosis of AF were included in this study. Patients were selected from the 2019 national inpatient sample. The primary outcome of interest was incidence of stroke. T-test was used to compare differences in continuous variables. For categorical variables, pearson chi-square was used to compare differences. Multivariate logistic regression was used to adjust for potential confounders. A 2-sided P&lt;0.05 was considered significant throughout the analyses. Results: This study included 45,102 AA female patients with AF, and 46,768 AA male patients with AF. In our study, female patients had higher prevalence of Hypertension (HTN) (22.3% vs 19.0, P&lt;0.001), Diabetes Mellitus (DM) (48.1 vs 46.0, P&lt;0.001), Obesity (27.8 vs 20.8), Hyperlipidemia (HLD) (50.9% vs 49.1%, P&lt;0.001), Hyperthyroidism (2.2% vs 1.2%, P&lt;0.001), and Chronic Obstructive Pulmonary Disease (COPD) (24.8% vs 23.2%, P&lt;0.001). AA female patients with AF experienced higher incidence of stroke compared to AA male patients with AF, (4.9% vs 4.1%, p-value &lt;0.001) and the odds of stroke also showed higher in female patients (aOR=1.10, 95% CI: 1.03-1.18, p &lt;0.005) after controlling for comorbidities. Only HTN and HLD showed statistically significant association with stroke in univariate analysis, (OR=2.02, 95% CI: 1.89-2.16 and OR=1.24, 95% CI:1.16-1.31, respectively) Conclusion: In our study, we identified that AA female patients with AF had a higher incidence of stroke compared to AA male patients with AF. Only HTN and HLD were significant risk factors contributing to the increased stroke incidence in the female group. The findings of our study are hypothesis-generating, and well-powered randomized controlled trials are needed to validate these findings.
Abstract 13857: Reduction of Infarct Size in Anterior ST Segment Elevation Myocardial Infarction (STEMI) With LAD Occlusion and LV Unloading Using a Micro-Axial Pump for 30 Minutes Before PCI: A Per Protocol Analysis of the STEMI DTU Pilot Study
Authors: Navin K Kapur, Jeffrey Moses, HAROON FARAZ, Zachary George, Vijay S Iyer, Amir Kaki, Richard Karas, Carey Kimmelstiel, Gerald Koenig, Ryan D Madder, Perwaiz M Meraj, Jason A MORELAND, Raymond J Kim, theodore schreiber, david wohns, James E Udelson, Gregg Stone, William O'Neill
Journal: Circulation (2022)

BACKGROUND: The STEMI-DTU pilot trial was the first exploratory study to identify that LV unloading and delaying reperfusion is safe and feasible in anterior STEMI without cardiogenic shock. We now report new findings in patients who met all protocol inclusion and exclusion criteria (per protocol cohort). Methods: In a multicenter, prospective, randomized safety and feasibility trial, we assigned 50 patients with anterior STEMI to LV unloading by using the Impella CP followed by immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). Cardiac magnetic resonance (CMR) imaging assessed infarct size normalized to the area at risk (IS/AAR) 3-5 days after PCI. Patients without CMR at 3-5 days (n=10; 5/arm), without PCI of a culprit LAD lesion (n=2; 1/arm) and without STEMI (n=5; 4 in U-IR, 1 in U-DR) were not per protocol and thus excluded from this analysis. Results: A total of 33 patients met all inclusion and exclusion criteria (U-IR n=15; U-DR n=18) with respective door-to-balloon times of 75±26 and 89±23 minutes (p=.10) and mean unload-to-balloon times of 10±5 and 34±3 (p&lt;0.01). In the total cohort, IS/AAR was significantly associated with microvascular obstruction (MVO), 30-day IS normalized to total LV mass, 90 day LVEF, and 90dday LV end systolic volume with or without a delay to reperfusion (Table, R&gt;0.5, p&lt;0.005 for all). Despite longer symptom to balloon times in the U-DR arm (174±59 vs 228±78, p&lt;0.01), IS/AAR was lower in the U-DR arm (62±16 vs 48±16, p=0.04) and remained significantly lower irrespective of the magnitude of precordial STE. MVO was significantly lower in the U-DR arm among patients with the highest precordial STE (Figure). Conclusion: A per protocol analysis of the STEMI-DTU Pilot trial identified a significant reduction in infarct size among patients with unloading and delayed reperfusion irrespective of precordial STE magnitude. These findings are currently under investigation in the STEMI-DTU Pivotal trial.
Abstract 12790: The Role of Social Determinants of Health in Rural Hf Outcomes
Authors: Lauren Gilstrap, Christopher Leggett, James O'Malley, Heather Carlos, Sandra Wong, sally kraft, Matthew Mackwood, Jonathan Skinner
Journal: Circulation (2022)

Background: Over 6.5 million Americans suffer from heart failure (HF) and 20% of these, 1.5 million Americans, live in rural areas. Compared to urban patients with HF, rural patients have higher rates of hospitalization and higher mortality. The reasons for these disparities are not well understood. In this study, we aimed to determine how much of the variation in urban/rural 30-day mortality could be explained by: 1) comorbidities; 2) guideline directed medical therapy (GDMT) use and 3) social determinants of health (SDOH). Methods: Using 100% Medicare Parts A and B and a random 40% sample of Part D, a cohort of 356,194 fee-for-service beneficiaries with ≥1 hospitalization for HFrEF between 2008 and 2016 was created. Rurality was determined using the beneficiaries’ ZIP code of residence and the Rural/Urban Commuting Areas (RUCA) classification. Hierarchical, logistic regression modeling, we then examined the association between 1) comorbidities; 2) GDMT use; and 3) the area deprivation index (ADI), a summary variable capturing multiple SDOH, and 30-day death after hospital discharge among HF patients in urban vs. rural areas. Results: When adjusting only for age, sex and race, rural patients have 15% higher odds of death (95% CI 12%, 19%, p&lt;0.001) in the 30 days after discharge for HFrEF. When comorbidities are added, the odd increase to 18% - an unexpected finding since comorbidity burdens are higher in rural areas. When GDMT use is added, the odds increase to 20%, also unexpected since prior work has shown GDMT is higher in rural areas. When ADI is added, the odds decrease to 14% (95% CI 10%, 18%, p&lt;0.001), suggesting that unlike comorbidities and GDMT use, ADI explains much of variation in urban/rural 30-day death rates. Conclusion: Living in a rural area is associated with a higher risk of 30-day death following a HFrEF hospitalization. Unlike comorbidities and GDMT use, SDOH appear to explain much of this difference in 30-day death rates.
Abstract 13446: Predicting Cardiovascular Risk and Preempting Major Cardiovascular Events During CAR T Therapy
Authors: Mahmoud Eljalby, Bradley Christensen, Anjali Rao, Edward Stephens, Alvin Chandra, Srilakshmi Vallabhaneni, Kathleen Zhang, Praveen Ramakrishnan, Larry Anderson, Gurbakhahs Kaur, Farrukh Awan, Vlad G Zaha
Journal: Circulation (2022)

Chimeric antigen receptor (CAR) T cell therapy is a breakthrough personalized, genetically engineered therapy that has been proven effective for the treatment of refractory multiple myeloma and large B cell lymphoma. However, significant major adverse cardiovascular events (MACE) have been reported with its application. To further investigate associated risk factors for MACE, we performed a retrospective analysis of a cohort of consecutive patients treated with CAR T therapy at our center. Clinical, laboratory and imaging parameters were collected for 48 patients. Of these, 7 patients (14.6%) had a MACE event. Variables analyzed included age, sex, body mass index, coronary artery calcium, lipid profile, baseline medications, preceding anthracycline or carfilzomib exposure, cancer type, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), tocilizumab, among others (Table). Peak C-reactive protein (CRP, median [IQR]) level was 76.00 (73.1) mg/dL in patients without MACE and 121.30 (133.22) mg/dL in patients with MACE, p = 0.028). CRS and ICANS grades were associated with MACE events ( p = 0.039 and 0.03, respectively). No echocardiographic differences were found. Our results indicate that the degree of inflammatory response, reflected by peak CRP level, is associated with MACE events in patients receiving CAR T therapy. These data suggest that inflammatory markers may be clinically relevant predictors of subsequent MACE complications in patients receiving CAR T therapy. Prospective inflammation monitoring and anti-inflammatory strategies may preempt MACE in this patient population.